Importance of this study
Introduction
Structure of B7-H3
Receptor of B7-H3
TLT-2
IL20RA
PLA2R1
B7-H3 and malignant behaviors
B7-H3 in cancer proliferation
B7-H3 in deregulating cancer metabolism
B7-H3 in cancer invasion
B7-H3 in cancer anti-apoptosis activity
B7-H3 in cancer therapy resistance
B7-H3 in cancer stem cells
B7-H3 and other cancer hallmarks
B7-H3 in the tumor microenvironment
B7-H3 and TME immune cells
B7-H3 and vascular network
B7-H3 and other TME characteristics
B7-H3 in different malignancies
B7-H3 in lung cancer
B7-H3 in CRC
B7-H3 in breast cancer
B7-H3 in prostate cancer
B7-H3 in melanoma
B7-H3 in gastric cancer
B7-H3 in liver cancer
B7-H3 in cervical cancer
B7-H3 in brain tumors
Cancer types | Authors | Year | Type of samples analyzed | Expression | Functions | References |
---|---|---|---|---|---|---|
Esophageal cancer | Chen et al. | 2015 | Cancer cell line and human esophageal cancer tissues | High B7-H3 expression in 97 out of 174 cancer tissues, correlated with poorer survival and invasion depth | B7-H3 expression inversely correlated with infiltrated T cells | [166] |
Merkel cell carcinoma | Aung et al. | 2019 | MCC cancer tissues | Consistent low expression of B7-H3 in MCC tumor cell, 9/20 strongly expressed in associated endothelial cells | Colocalization of endothelia CD31 expression and B7-H3 expression is a poor prognostic indicator | [167] |
Ovarian cancer | Cai et al. | 2020 | Ovarian cancer xenograft model | B7-H3 robustly expressed in 24 ovarian cancer tissues | B7-H3 inhibits CD8+ T cell function, correlates with T cell exhaustion, which can be reversed by targeting B7-H3 in murine model | [99] |
Acute myeloid leukemia | Lichtman et al. | 2021 | AML cell lines, primary AML blast, normal bone marrow and xenograft models | B7-H3 is highly expressed on monocytic AML cell lines and primary AML blasts from patients | B7-H3 CAR-T showed potent anti-AML effect in vitro and in xenograft model | [168] |
Pancreatic cancer | Si et al. | 2022 | Pancreatic adenocarcinoma tissues | High B7-H3 expression in 52/104 cases, verified in TCGA data | High B7-H3 expression correlates with poor differentiation level, predicts a poor prognosis | [169] |
Urothelial carcinoma | Koyama et al. | 2020 | Urothelial carcinoma tissues | B7-H3 expression was observed in 36 of 271 (13%) cases | B7-H3 expression was significantly associated with shorter PFS, disease-specific survival, tumor stage, grade and lymph node involvement | [170] |
Laryngeal squamous cell cancer | Li et al. | 2021 | LSCC tissues and adjacent tissues | 75/122 (61.5%) stained strongly positive for B7-H3, verified by RNA seq and TCGA data | B7-H3 overexpression significantly correlated with poor OS and lower TIL density | [171] |
Skull base chordoma | Long et al. | 2021 | Chordoma samples and B7-H3 positive cell lines | B7-H3 positively was observed in 7 out of 45 (16%) chordoma samples | B7-H3 CAR-T showed potent anti-chordoma effect in vitro | [172] |
Immunotherapy targeting B7-H3
Trial number | Intervention | Intervention type | Phase | Status | Cancer type |
---|---|---|---|---|---|
NCT04145622 | DS-7300a | B7-H3 ADC | I/II | Recruiting | Advanced solid tumors |
NCT05280470 | DS-7300a | B7-H3 ADC | II | Recruiting | Extensive-stage small cell lung cancer |
NCT03729596 | MGC018/ MGA012 | Anti-B7-H3 ADC with Anti-PD-1 Ab | I/II | Recruiting | 6 advanced solid tumors |
NCT02192567 | DS-5573a | B7-H3 ADCC | I | Terminated | Advanced solid tumors |
NCT01391143 | MGA271 | B7-H3 ADCC | I | Completed | Prostate cancer, melanoma, renal cell carcinoma, triple-negative breast cancer, head and neck cancer, bladder cancer and NSCLC |
NCT02982941 | MGA271 | B7-H3 ADCC | I | Completed | Solid tumor |
NCT02923180 | MGA271 | B7-H3 ADCC | II | Active, not recruiting | Prostate cancer |
NCT02381314 | MGA271/Ipilimumab | Anti-B7-H3 ADCC with Anti-CTLA-4 Ab | I | Completed | Melanoma and NSCLC |
NCT04630769 | MGA271/ FT516 and IL2 | Anti-B7-H3 ADCC with NK cell enhancing | I | Recruiting | Ovarian cancer |
NCT04634825 | MGA271/MGA012/MGD013 | Anti-B7-H3 ADCC with Anti-PD-1 Ab or PD-1 X LAG-3 BiAb | II | Terminated | Head and neck cancer |
NCT02475213 | MGA271/pembrolizumab/MGA 012 | Anti-B7-H3 ADCC with Anti-PD-1 Ab | I | Completed | Melanoma, head and neck cancer, NSCLC, urothelial carcinoma |
NCT02628535 | MGD009 | B7-H3 X CD3 BiAb | I | Terminated | Mesothelioma and 11 other cancers |
NCT03406949 | MGD009/ MGA012 | B7-H3 CD3 BiAb with Anti-PD-1 Ab | I | Active not recruiting | Advanced solid tumors |
NCT04432649 | 4SCAR-276 | CAR T cells | I/II | Recruiting | Solid tumor |
NCT05143151 | CD276 CAR-T | CAR T cells | I/II | Recruiting | Advanced pancreatic carcinoma |
NCT04637503 | Combined 4SCAR-276 | CAR T cells | I/II | Recruiting | Neuroblastoma |
NCT04864821 | B7-H3 CAR-T | CAR T cells | I | Not yet recruiting | 4 solid tumors |
NCT04185038 | SCRI-CARB7H3 | CAR T cells | I | Recruiting | Central nervous system tumors |
NCT04691713 | B7-H3 CAR-T | CAR T cells | Not applicable | Recruiting | Solid tumor |
NCT04385173 | B7-H3 CAR-T | CAR T cells | I | Recruiting | Recurrent/refractory glioblastoma |
NCT04670068 | B7-H3 CAR-T | CAR T cells | I | Recruiting | Recurrent epithelial ovarian cancer |
NCT04483778 | 4-1BBζ B7H3-EGFRt-DHFR | CAR T cells | I | Recruiting | Recurrent/refractory solid tumors |
NCT04077866 | B7-H3 CAR-T | CAR T cells | I/II | Recruiting | Recurrent/refractory glioblastoma |
NCT05241392 | B7-H3 CAR-T | CAR T cells | I | Recruiting | Glioblastoma |
NCT04897321 | B7-H3 CAR-T | CAR T cells | I | Recruiting | Pediatric solid tumor |
NCT05211557 | fhB7-H3 CAR-T | CAR T cells | I/II | Recruiting | Recurrent ovarian cancer |
NCT03198052 | B7-H3 and 10 other CAR-T | CAR T cells | I | Recruiting | Lung cancer |
NCT04842812 | B7-H3 and 11 other engineered CAR-T | CAR T cells | I | Recruiting | Advanced solid tumors |
NCT05190185 | TAA06 | CAR T cells | I | Recruiting | Malignant melanoma, lung cancer, or colorectal cancer |
NCT04692948 | TAA06 | CAR T cells | Not applicable | Recruiting | Acute myeloid leukemia |
NCT01502917 | 124I-omburtamab | Radioimmunotherapy | I | Terminate | Brain cancer |
NCT00089245 | 131I-omburtamab | Radioimmunotherapy | I | Active, not recruiting | Neuroblastoma, sarcoma and CNS tumors |
NCT01099644 | 131I-omburtamab | Radioimmunotherapy | I | Active, not recruiting | Peritoneal cancer |
NCT03275402 | 131I-omburtamab | Radioimmunotherapy | II/III | Recruiting | Neuroblastoma, CNS and leptomeningeal metastases |
NCT05063357 | 131I-omburtamab | Radioimmunotherapy | I | Not yet recruiting | Diffuse intrinsic pontine glioma |
NCT04022213 | 131I-omburtamab | Radioimmunotherapy | II | Recruiting | Peritoneum solid tumors |
NCT04743661 | 131I-omburtamab | Radioimmunotherapy | II | Active, not recruiting | Recurrent medulloblastoma and ependymoma |
NCT04315246 | 177Lu-DTPA-omburtamab | Radioimmunotherapy | I/II | Recruiting | Leptomeningeal metastasis solid tumor |
NCT04167618 | 177Lu-DTPA-omburtamab | Radioimmunotherapy | I/II | Recruiting | Medulloblastoma |
Agent | Agent type | Trial ID | Type of study | Cancer types | Enrollment | Study design | Main conclusion | References |
---|---|---|---|---|---|---|---|---|
MGC018 | ADC | NCT03729596 | Phase I/II clinical trial | HNSCC, TNBC, melanoma, NSCLC, metastatic castrate-resistant prostate cancer (mCRPC) | 80 | Open-label dose escalation + cohort expansion | 49/80 of the enrolled pts took 3 mg/kg MGC018 as determined in dose escalation study. 87.7% encountered at least 1 adverse event, most commonly neutropenia, fatigue, palmar-plantar erythron dysesthesia and headache. PSA decline and tumor regression was observed in prostate cancer pts | |
DS-7300 | ADC | NCT04145622 | Phase I/II clinical trial | 11 advanced solid cancers | 127 | Open-label dose escalation + cohort expansion | Treatment-emergent adverse events occurred in 124/127 pts (98%); the most common were nausea (61%), infusion-related reaction (35%), and vomiting (31%). Responses were observed in 30/91 evaluable pts (33%) in total, 7/9 pts with SCLC, 2/5 with NSCLC, and 16/42 with mCRPC | [179] |
MGA271 | ADCC | NCT01391143 | Phase I clinical trial | 7 advanced solid cancers | 46 | Open-label single-arm | MGA271 was well tolerated, with no dose-limiting toxicity. Pts experienced disease stabilization (> 12 weeks) and tumor shrinkage (2–69%) across several tumor types | [182] |
MGA271 | ADCC | NCT02923180 | Phase II clinical trial | Prostate cancer | 32 | Open-label single-arm | 12% of the enrolled pts experienced grade 3/4 adverse events. Post-treatment PSA declines, PSA0 at 1-year post-op, Gleason grade group changes showed promising results. Pathologic and immunologic evaluation of prostate revealed upregulation of CD8+ T cells, PD-1/PD-L1 expression, and immune activation | [183] |
MGA271 + pembrolizumab | ADCC | NCT02475213 | Phase I/II clinical trial | Advanced solid tumors | 133 | Open-label dose escalation | 116/133 pts experienced treatment-related adverse events, 38/133 ≥ grade 3. Objective response was observed in 6/18 pts with HNSCC and in 5/14 pts with NSCLC, 1/17 patients with urothelial cancer and 1/13 pts with melanoma. Pts with previous ICI treatment had a poorer prognosis | [127] |
B7H3 CAR-T | CAR T cells | ChiCTR1900023435 ChiCTR2100044386 | Case reports | Meningioma, glioblastoma and basal cell carcinoma | – | Case reports | CAR-T infusion was well tolerated in three cases. No obvious therapy response was observed in meningioma and glioblastoma cases. Partial response in basal cell carcinoma case | |
4-1BBζ B7H3-EGFRt-DHFR | CAR T cells | NCT04483778 | Phase I clinical trial | Relapsed/ refractory non-CNS tumors in pediatric or young adult patients | 16 | Open-label non-randomized two arms | No dose-limiting toxicity was observed in the first infusion, maximum circulating CAR-T expansion on first infusion was 4.98 cells/μL with median persistence of 28 days. Stable disease was observed in 3 of the 9 pts infused | [199] |
131I-Omburtamab | Radioimmunotherapy | NCT00089245 | Phase I clinical trial | Recurrent or metastatic neuroblastoma | 105 | Open-label single-arm | Self-limited fever, nausea and headache, creatinine elevation, and grade 1 and 3 transient elevated serum transaminase was observed. Nearly 50% of pts survive at least 36 months. Over 50% of pts were still alive when data was last updated | |
131I-Omburtamab | Radioimmunotherapy | – | Clinical retrospective analysis | Recurrent rhabdomyosarcoma | 23 | Retrospective review | A prolonged survival of pts receiving intraventricular 131I-Omburtamab (P = 0.003) | [205] |
124I-Omburtamab | Radioimmunotherapy | NCT01502917 | Phase I clinical trial | Diffuse intrinsic pontine glioma in children | 46 | Open-label dose escalation | 10/46 enrolled pts experienced grade 3 adverse events considered related to the agent. A dose up to 8 mCi and infusion volume of 8 mL were found to be safe. The median survival increased 3–4 months compared to historical control data |